This application for a K23 Career Development Award proposes a four-year program to provide the candidate with mentored training in patient-oriented research, protected time, and coursework in advanced epidemiology, biostatistics, and community-based participatory research. The long- term goals of the candidate are to become an independent physician-scientist at an academic medical center, investigating the epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA- MRSA) and the molecular mechanisms driving staphylococcal transmission, leading to the development of novel methods for the prevention and treatment of CA-MRSA infections. The proposed work will be performed at Washington University and St. Louis Children's Hospital under the mentorship of Victoria Fraser, M.D., an accomplished clinical investigator in infectious diseases epidemiology. A faculty advisory committee consisting of experienced clinical and basic researchers will facilitate the candidate's research and career development. Epidemic strains of CA-MRSA cause significant morbidity and mortality among immunocompetent individuals, especially children, ranging from superficial cutaneous abscesses to invasive infections. CA- MRSA infections have been observed to cluster in households. However, the interplay of household colonization pressure and transmission, hygiene and behavioral risk factors, and environmental contamination influencing CA-MRSA colonization and infection has not been specified. These risk factors must be defined to develop evidence-based guidelines to interrupt CA-MRSA transmission and prevent infections. Understanding the impact of these variables will inform practice to improve health and decrease the burden of CA-MRSA colonization and disease. Preliminary studies demonstrate that household members of index patients with CA-MRSA infection and colonization are also colonized with CA-MRSA. A one-year prospective cohort study of 135 pediatric patients with CA-MRSA infection and their household members will be performed. Using mixed effects logistic regression modeling, the relationships among risk factors at multiple levels (including household colonization pressure, host behavioral practices, and contamination of household surfaces) will be elucidated to identify factors conferring the greatest risks for CA-MRSA colonization, infection, and transmission. Three integrated specific aims are proposed: 1) Define the transmission dynamics of CA-MRSA colonization and infection among pediatric index patients and their household contacts over one year, and determine the contribution of CA-MRSA colonization to subsequent CA-MRSA infection; 2) Identify hygiene and behavioral practices contributing to CA-MRSA transmission, colonization, and infection within households; and 3) Determine the role of environmental contamination and household characteristics in household CA-MRSA transmission. PROJECT NARRATIVE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant public health problem causing infections in healthy people. The proposed research will define how CA-MRSA is transmitted within households and identify risk factors for colonization and infection. The results will be used to design interventions to prevent CA-MRSA infections.